The long term goal of this proposed research is to determine the role of soluble macrophage products in host defense against tumors and infectious agents. Our animal studies are based on the observation that macrophages activated in vivo with intracellular parasites release a soluble product in in vivo cultures that kills certain tumor cells and some species of micro-organisms. In human systems, we will attempt to show whether normal monocytes activated in vitro release similar materials. Specifically, we will (1) further purify and define the role of soluble products in macrophage-mediated cytotoxicity, (2) analyze the mechanisms of action of these materials on tumor and bacterial cells, and (3) examine if soluble products contribute to the expression of human monocyte cytotoxicity.